Asthma is the epidemic of the new millennium. Despite the increase in our knowledge, the morbidity, mortality and prevalence of asthma and other allergic diseases are increasing as shown by WHO statistics. (1)
Barnes J December 1999, review the current state of anti-asthma therapy, over the past 10 years there have been striking improvement in the treatment of asthma largely as a result of the earlier and more widespread use of inhaled corticosteroids. The developments of new treatments for asthma has proved difficult, although several immunologic approaches are undergoing preclinical and clinical assessment. Antileukotrienes are the only new class of drugs to treat asthma that have been introduced in the past 25 years, but their efficacy is somewhat limited and unpredictable, as compared with that of inhaled corticosteroids. (2)
The main disadvantages associated with inhaled corticosteroids is that it should be used on day-to-day bases, alternate day steroid therapy is unable to control the disease (British National Formulary). Four weeks treatment with recommended dose of corticosteroids is associated with significant increase in peak expiratory flow rate, and decrease the need for rescue salbutamol use in asthmatic subjects, but was not associated with large reductions in markers of eosinophilic inflammation, bronchovascular permiability, or mucus hypersecretion. Alternative therapies for corticoseroid-dependant asthma, such as methotrexate, cyclosporine and oral gold, are problematic and have high incidence of adverse effect. (2)
2-Immunological therapy: in the form of allergen immunotherapy is the only therapeutic modalities which have the potential to modify the natural course of the disease, hence, immunotherapy is a preventive and curative treatment, mostly by inducing immune deviation (upregulation of a distinct subset of Th0/Th1 cells). It is a cumbersome therapy.
There is accordingly an outstanding need for an effective and convenient means for treating and/or preventing type I IgE-mediated hypersensitivity reactions, including asthma, in mammals.
1—Glycophosphopeptical: The present inventor has, surprisingly, found that a short-term administration of Glycophosphopeptical (Glicofosfopeptical) to patients suffering from asthma is capable of treating and/or preventing asthma, Glycophosopeptical is marketed under the trade names “IMMUNOFERON” and “INMUNOFERON” drug by Industrial Farmaceutica Cantabria, S.A. (Spain), Glycophosopeptical is a GLUCOMANNAN from Candida utillis to be used as an immnostimulant for oncology, secondary immunodeficiency, and stimulating cell mediated immunity. It is not indicated for the treatment of diseases caused by type I hypersensitivity and asthma defined
Of particular interest was the clinical effect of Glicophosphopeptical treatment in chronic bronchitis patients, which resulted in significant increases in the number of monocytes as well as their phagocytic and chemotactic activity. The depressed number of natural killer cells was reversed to near their levels in young healthy adults. These observations help to explain how glycophosphopeptical aids in the restoration of natural cellular immunity and its possible application as an adjuvant to bacterial & viral vaccines as well as in the treatment chronic bronchitis. (3)
Inmunoferon enhances the activities of early-type interferon inducers and natural killer cells, although it is not an interferon inducer by itself. (4)
Intraduodenal administration of a phosphorylated glycomannan-protein fraction of the cell wall of Candida albicans resulted in a significant increase in Interferon response in the abdominal lymph in rabbits immunized against Candida albicans. Antiviral activity was absent in plasma in all cases. (5)
Glocomannan-containing antiobesity pharmaceuticals due to delayed food digestion in the stomach. (6)
Pharmaceutical application of Konjac glucomannan. (30)
The immunologic enhancement activity of dicarboxy glucomannan was evaluated in vitro by determining glucose conumption and beta-glucuronidase activity in cultured macrophages. (31)
2—Nigella sativa: Herbs are highly desired as a “natural” way to treat a disease. Some preparations have been known for literally thousands of years while others are just being discovered to have curative effects
Nigella sativa, also known as black cumin, is a well-known herb, and its seeds are widely available for use as a spice or condiment. Nigella sativa is folk medicines, treating many diseases including many with respiratory symptoms.
Medenica R D (1995) disclose the use of N. sativa as a medicinal treatment, providing an anticancer remedy and treatment which has, as its active ingredient, the extract of the plant N. sativa. When used properly, the medicament of the present invention is useful in treating cancer at a concentration which is effective to destroy cancer cells in a patient, preventing toxicity of anticancer drugs in human body, and in increasing immune function, and as a growth factor for bone marrow in hematopoiesis. Also directed to a method for protecting the normal cells from cytopathic effects of virus. The effective dose is about 30 grams of the extract per day, the concentration of the extract from Nigella sativa is sufficient to reduce the presence of one or more factors normally present in the human body, the factors being selected from the group consisting of interferon inhibitor factor and lymphokine inhibitor factor. (7)
Shawkat (1989) describe an extract solution and herbal mixture for treatment of Hepatitis-B and Hepatitis-C, containing Nigella sativa L in a mixture with 9 other herbs. (8)
The following studies are considered relevant to the relation between N. sativa and asthma: Sayed 1980: The oil is used in the treatment of asthma, respiratory oppression and coughs. The active principal, nigellone, has been isolated from the volatile oil fraction and is reported to be useful in the treatment of bronchial asthma. (9)
Mahfouz M and El-Dakhakhny M 1960: The chemical and pharmacological properties of the new anti-asthmatic drug, nigellone. (10)
El-Tahir et al 1993: The respiratory effect of the volatile oil of the black seed (Nigella sativa) in guinea-pig: elucidation of the mechanism (s) of action. (11)
Aqcl M B 1992 The calcium antagonistic effect of the volatile oil of Nigella sativa seeds. (12)
Reicex M, Brandt W 1985: The relaxant effects of N sativa on tracheal and ileal smooth muscles of the guinea-pig. (13)
Elkadi A and Kandil O, 1987: Nigella sativa and Immunity Its Effects increase CD4 (helper) T cell population. (14)
Boskababy & Shahabi, 1997: Bronchiodilatory and Anticholinergic effects of Nigella sative. (15)
Mutabagani & El-Mahdy, 1997: A study of the Anti-inflammatory activity of Nigella sativa. (16)
3—Bacillus Calmette Guerin (BCG): is a strain of mycobacterium used to induce immunity to tuberculosis by stimulating Cell Mediated Immunity mediated by T lymphocytes (Th1). The relation of BCG vaccination to asthma is a debate.
BCG has also been used as a therapeutic agent in the treatment of cancer, inducing Cell Mediated Immunity when given as a systemic or intralesionl injection, (17, 18, 19). BCG is also used to treat viral warts that are resistant to other forms of therapy
T lymphocyte stimulation in culture is an in vitro correlate of cell mediated immunity. An evaluation of the effect of N. sativa on T lymphocytes in culture indicated that the water extract, chloroform extract and oil layer of N. sativa each show similar activity to preparations of a known standard antigen purified protein derivative from BCG.
Measles or rubella infection can cause tuberculin positive patients to revert temporarily and become tuberculin negative. (20) Therefore viral infections in general, benefits from BCG-like Th1 stimulation as described by this invention.
4—The role of cytokines in allergic inflammation and cell recruitment:                Currently, IgE production is under the control of Interleukiens produced by T-helper 2 lymphocyte, allergy is clearly a Th2 disease.        Eosinophilia is a consistent and characteristic feature of airway mucosa of late-phase asthmatic response to allergen. IL-3, IL-5 and GM-CSF are eosinnophil active cytokine.        Asthma is an inflammatory mediator soup. (21)        Th1 cells develop in the presence of a large range of antigens associated with delayed hypersensitivity response like tuberculosis, sarcoidosis, leprosy, and viruses, generates predominantly IFN gamma which inhibits the differentiation and production of cytokines by Th2 and vice versa. (21, 22, 23, 24, 25)        
5—My novel concept in immunopathology of allergy.
A normal person is in a state of “Tolerance to Environmental Antigen, TEA”.
Pre-inflammatory phase of allergy is controlled by Th1 cells, and it's cytokine interferon. This is based on my discovery that interferon is a potent Eosinophil Chemotactic Factor.
TH1 suppression is the cause of allergy. Manifested by low serum interferon in acute asthmatic attacks. (26, 27)
Th1 stimulation is capable of selectively switch-off the eosinophilic airway inflammation, normalizing serum interferon This can be achieved by using a novel class of asthma therapy, which is the subject of this invention. “days” therapy with a BCG-like Th1 stimulation  long term clinical remission